Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• commercially available benzonitriles [39] or by thionation of the corresponding N-substituted amides [40] using pyridine–P4S10 as sulfurization agent. Other chemicals and solvents were purchased from Acros Organics, Sigma-Aldrich, and Fluorochem and were used as received. 1H and 13C (APT) NMR spectra were

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• the thioamide functionality including base-catalyzed Willgerodt–Kindler reaction [54], Kindler reaction in the presence of sulfated tungstate [55], thionation of amides using thionating reagents [56] and thionation of amides using TsCl (4-toluenesulfonyl chloride) or PSCl3-mediated Beckmann

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• . The resolution of compound 1 was not conducted at this point because its synthesis was deemed problematic. While relatively short (5 steps), the overall yield was only 20% due to a low-yielding key step and a problematic thionation step immediately following. Unfortunately, thionation of 8 with an

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• derivatives 27–30 were prepared from 8, 20, 21, and 26 using microwave heating with Lawesson’s reagent and HMDO (Scheme 6). Thionation provided the title compounds in good to high yields. Biochemical study – AchE inhibition The compounds were further tested for their ability to inhibit AChE in vitro [24

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• alkylation of the anion of pyrrolidin-2-one (16) with ethyl bromoacetate to afford the known compound ethyl 2-(2-oxopyrrolidin-1-yl)acetate (17) [31][32][33] in 77% yield. Thionation of 17 with Lawesson’s reagent in toluene at 80 °C gave the thione 18 as a yellow oil (86%). Reaction of 18 with phenacyl

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• ; thioamide; thionation; Introduction The transformation of a carbonyl into a thiocarbonyl group is one of the most important reactions in organic synthetic chemistry [1]. Lawesson’s reagent (LR) is widely applied in this transformation, as well as for the syntheses of various sulfur-containing heterocyclic

• compounds [2][3][4][5]. Although LR is a powerful, mild and versatile thionation reagent, the workup procedures of reactions involving this reagent have received quite a few negative comments [6][7][8][9][10]. The reason for this is that an inherent six-membered ring structure A (Figure 1) is formed from

• thionation reactions, considerable efforts have been devoted to the improvement of the workup procedures of these reactions. For example, Soós and co-workers introduced perfluoroalkylated derivatives of LR, which simplified the product isolation via a fluorous reversed-phase solid extraction technique [9][10

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• also Supporting Information File 1). The primary thiobenzamides 2a–d were prepared by the magnesium chloride-catalyzed thiolysis of commercially available benzonitriles [53] and the secondary thiobenzamides 3a–h were obtained by the thionation of the corresponding N-substituted amides [54] using

• pyridine–P4S10 as sulfurization agent. The tertiary thiobenzamides 4a–c were synthetized by a one-pot acylation/thionation from the corresponding acid chlorides and dimethylamine [55]. Other chemicals and solvents were purchased from Acros Organics, Sigma-Aldrich, or Fluorochem and were used as received

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• capillaries with a Melt Temp II apparatus. Starting materials: D–A cyclopropanes 5a–g were obtained following the reported procedure [28]. Ferrocenyl thioketones 8a–g were obtained by thionation of corresponding ferrocenyl ketones [29] by treatment with Lawesson’s reagent [30]. Ferrocenyl β-naphthyl

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• -substituted tetrahydro-1,3-thiazepines by MW-assisted cyclization of 4-thioamidobutanols is presented. The acyclic precursors were prepared in high overall yields by an expeditious three-step diacylation/thionation/deprotection sequence from 4-aminobutanol. Microwave-assisted ring closure of 4-thioamido

• -hydroxybutyl)thioamides promoted by PPA esters. The preparation of these acyclic precursors is not straightforward, as it involves a selective thionation step. We present herein a novel method for the synthesis of seven-membered cyclic iminothioethers from commercially available 4-aminobutanol. The sequence

• thionation of the corresponding 4-amido alcohols cannot be used, as the OH is almost as reactive as the amide carbonyl toward Lawesson's reagent, the most commonly used thionating agent [56]. Two syntheses of ω-thioamidobutanols were recently reported by Nguyen et al. The first one afforded N

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• isoamyl nitrate [35] or, as in the case of 2b, by oximation of 1,2-diphenylethane-1,2-dione [36]. 2,2,4,4-Tetramethylcyclobutane-1,3-dithione (11a) was prepared from the dimethylketene dimer (2,2,4,4-tetramethylcyclobutane-1,3-dione) by thionation using tetraphosphorus decasulfide [37]. Adamantan-1-yl

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• thiodibenzosuberone (1i) were prepared from the corresponding ketones by treatment with Lawesson’s reagent (L.R.) in toluene upon irradiation with microwaves (150 W) over 2 min [32]. The most efficient method for the preparation of thiofluorenone (1c) was the thionation of fluorenone by simultaneous passing of dry

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• group as thionation could also be effected at the amide [100], so somewhat limiting the saccharide scope of this chemistry. We feel that a follow-up study providing the protecting-group-free access to the purified protein would be of great importance. 4.5 pH-Specific activation Protecting-group-free

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• the tolerance of reducible functional groups like a nitro group and a triple bond in the reaction which cannot be used in the reported methods. A hypothetical mechanism (Scheme 2) for this conversion was believed to involve, in analogy with the thionation of nitriles to thioamides [20], initial

• thionation of the thiocyanate functionality with P2S5 to give the corresponding dithiocarbamate derivative which, in presence of residual phosphoric acid of P2S5, decomposes to give the corresponding thiol, in analogy with the acidic hydrolysis of S-thiocarbamates [21]. Although, we were not able to isolate

• thionation of benzyl S-thiocarbamate led to the formation of benzyl S,S-dithiocarbamate which underwent acidic hydrolysis to give the corresponding thiol. Conclusion In summary, the method described in this paper presents an efficient and direct route for the conversion of organic thiocyanates to the

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• microwave assistance (Scheme 1). Thionation of the 4-position of 1, 4, 6, 10, 13 and 15 using P4S10 in pyridine under reflux conditions gave the 4-thiones 2, 5, 7, 11, 14 and 16 in yields between 60–80%, respectively (Scheme 1). The HHQ-oxime (3) was synthesized from HHQ (1) by conversion in the benzyl

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• Carius tube at 250 °C, affording alcohol 5 in 81% yield. The subsequent protection of the primary alcohol as acetate 6 (87% yield), followed by thionation with phosphorus pentasulfide using the Brillon procedure [29] afforded thiolactam 3 in 90% yield. The succeeding Eschenmoser reaction with α

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• indolin-2-ones 11. Compounds 11 bearing the fragment of 4-oxobutyramides (1,4-dicarbonyl derivatives) can be cyclized into thieno[2,3-b]indoles by using the Paal–Knorr reaction with such thionation agents, as P4S10 or Lawesson’s reagent. This four-step route to thieno[2,3-b]indoles via the formation of

• ellipsoids of 50% probability are presented. Synthetic routes to thieno[2,3-b]indoles. Synthesis and thionation of indodin-2-ones 11. Synthetic paths to thieno[2,3-b]indole 12a. LR = Lawesson's reagent Two-step synthesis of 2-(hetero)aryl substituted thieno[2,3-b]indoles 12. Synthesis of mono- and dibromo

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• addition followed by dimethylamine absorption then affords the observed thiazoles (((1-thiazole-2-yl)methyl)azetidin-2-ones) in moderate to good yields (36–69%). In contrast, Thompson et al. described the synthesis of 2,4-disubstituted 5-aminothiazoles via a sequential Ugi/deprotection/thionation

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• /bjoc.8.181 Abstract Dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives were prepared by successive N3- and N1-alkylation of hydantoins, followed by regioselective thionation and subsequent cyclization under mild conditions. In a final alkylation step a further substituent may be

• - and chemoselective reaction; thionation; X-ray structure; Introduction Imidazotriazines represent an important class of condensed heterobicycles that display a variety of significant biological activities, including anticancer [1], antimicrobial [2], anti-inflammatory [3] and neuroprotective [4

• thioketones 20–22 may be due to electronic effects and prevention of the formation of certain tautomers by the C4-methyl groups in compounds 13–15 [22]. To investigate the influence of the C4-methyl groups on the regioselective thionation reaction, we treated unsubstituted 5,5-dimethylhydantoin 6 with

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• ), and Boc-Gly9ψ[CS-NH]Ile-Leu11-OMe (for the preparation of ψ[CS-NH]9). Thionation of a peptide as short as a dipeptide is not recommended because a further synthetic step at the C-terminus of this compound would not take place satisfactorily, owing to the easy formation of a poorly reactive 1,3

• -thiazolidin-5-one. All thionation steps were conducted by use of the Lawesson's reagent under mild conditions (in tetrahydrofuran at room temperature) [53][54][55][56]. The only synthetic problem was identified in the preparation of the Fmoc-Gly5ψ[CS-NH]Gly-Leu-Aib8-Ot-Bu, in which case the thionation

• 9:1; Rf2: 1-butanol/acetic acid/water 3:1:1; Rf3: toluene/ethanol 7:1. General procedure for thionation of peptides To a solution of the peptide (1 mmol) in anhydrous tetrahydrofuran under nitrogen atmosphere, the Lawesson's reagent (0.6 mmol) was added. The reaction mixture was stirred at rt

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• lactam (+)-26 was troublesome, giving at best a yield of 52% when performed with sodium hydride and tetrabutylammonium iodide in N,N-dimethylformamide. An effortless thionation of 26 with Lawesson's reagent in boiling toluene produced the thiolactam (+)-27 in 92% yield. Eschenmoser sulfide contraction

• adding potassium tert-butoxide to a solution of the bromoamide in dry tetrahydrofuran at room temperature, a yield of 81% being obtained by keeping the reaction time short (25 min). To our dismay, however, the attempted thionation of 34 with Lawesson's reagent under a variety of conditions was uniformly